The present invention relates to leukocyte filters and filtration generally.
Filters are commonly used to remove leukocytes from blood and blood products in order to minimize various adverse effects of white cell transfusion. Examples of adverse effects include non-hemolytic febrile reaction, alloimmunization and graft versus host disease. Commercial leukoreduction filters are mostly composed of non-woven materials, which are made up of discrete fibers bonded or pressed together.
Another filter known in the art is a membrane filter, which, instead of having discrete fibers, is a continuous structure containing a network of pores. The membrane enables efficient capture of leukocytes and a reasonably good passage of the desired blood components (e.g., erythrocytes, platelets or plasma). However, membrane filters known in the art are either lacking in performance or require specific materials of construction, unusual pore morphology, a very narrow pore size distribution or pore size gradation within the filter.
One example of a membrane filter is described in U.S. Pat. No. 5,895,575 assigned to the present applicant/assignee, the disclosure of which is incorporated herein by reference. The ""575 patent describes a filter composed of nitrocellulose membranes and non-woven materials.
U.S. Pat. No. 5,476,587 (Kuroki et al.) describes a membrane with a most frequent pore diameter of 1-5 xcexcm, and a pore size weight average to number average ratio of 1.5 to 2.5, the ratio gradually changing from the top to the bottom of the filter.
U.S. Pat. No. 5,707,526 (a continuation-in-part of Kuroki et al.""s ""587 patent) describes a membrane having a most frequent pore diameter of 1-5 xcexcm, and a specific dust permeability, enclosed in a housing of a specially designed structure.
U.S. Pat. No. 5,478,470 (Fukuda et al.) describes membranes with a specific set of properties, including pores of 2-30 xcexcm having a combined pore volume equal to or greater than 94% of the total pore volume.
U.S. Pat. No. 5,665,233 (a division of Fukuda et al.""s ""470 patent) describes the use of porous materials, including membranes, having a specific set of properties, among them certain pore volumes, pore size gradation, leukocyte retention per layer, and layer thickness of less than 0.5 mm.
European Patent Application Publication No. 0406,485 A1 (now abandoned) describes membrane containing filters, wherein the membranes are strongly asymmetric, having a median pore size at the upstream surface substantially larger than at the downstream surface.
Japanese Patent Application No. 526,2656 describes membranes with a negative charge. Japanese Patent Application No. 503,4337 describes membranes made specifically of polyvinyl format or polyurethane. Japanese Patent Application No. 514,8150 describes a filter containing both porous materials and a non-woven fabric with fibers of 0.8-3 xcexcm diameter. Japanese Patent Application No. 54-44270 (filed Apr. 13, 1979) describes a polyester foam used to trap leukocytes.
Other membrane filters are described in European Patent Publication No. 408,462 B1 and U.S. Pat. No. 5,234,593, both of which have unusual pore structures, and in U.S. Pat. Nos. 4,985,153 and 5,783,094. The disclosures of all publications mentioned in the present specification are incorporated herein by reference.
In general in the prior art, membrane filters are constructed of specialized or non-commercial materials with narrow ranges of pore sizes. In addition, the filters generally have a non-homogeneous pore structure throughout their bulk, i.e. they employ membranes wherein the pores of the membranes have large diameter on one side of the membrane and a narrower diameter on the other side. Also, it has been assumed in the prior art that in order to obtain good throughput and prevent filter clogging, the filter must have a multilayer structure with a gradual decrease in pore size in the direction of flow.
The present invention seeks to provide an improved leukocyte filter, a filtering method and a filtered blood product, including a filtered whole blood product.
There is thus provided in accordance with a preferred embodiment of the present invention a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, the membrane filter portion having a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided, in accordance with a preferred embodiment of the invention, a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, the prefilter portion being characterized in that it captures less than 60% of incoming leukocytes, and the membrane filter portion being characterized in that it is non-cellulosic and generally homogeneous. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter portion comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided, in accordance with a preferred embodiment of the invention, a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, said membrane filter portion being characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that the cumulative surface area of pores having a pore diameter of 2-30 microns is less than 30% of the total surface area of the membrane. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter portion comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter portion comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, said membrane filter portion being characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane.
There is also provided in accordance with a preferred embodiment of the invention, the a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, said membrane filter portion comprising at least one layer of a generally homogeneous non-cellulsoic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention, a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, said membrane filter portion having at least 40% of its pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, said membrane filter portion having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, said membrane filter portion having no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter which captures less than 60% of incoming leukocytes; and supplying prefiltered blood products to a non-cellulosic and generally homogeneous membrane filter; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane mass ratio layer than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the non-cellulosic membrane is a generally homogeneous membrane. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter comprising at least one layer of a non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the coment of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter. In accordance with a preferred embodiment of the invention, the non-cellulosic membrane is a generally homogeneous membrane. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter having at least 5% of its pore volume constituted by pores having a pore cross section diameter larger than 10 microns; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that no more than 30% of its pore volume is constituted by pores having a pore cross section diameter less than 3 microns; wherein said blood product to be filtered of leukocytes has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtered blood product produced by a method including: supplying a blood product to be filtered of leukocytes to a prefilter which captures less than 60% of incoming leukocytes; and supplying prefiltered blood product to a non-cellulosic and generally homogeneous membrane filter; wherein the leukocyte filtered blood product has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtered blood product produced by a method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume; wherein the leukocyte filtered blood product has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtered blood product produced by a method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane; wherein the leukocyte filtered blood product has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtered blood product produced by a method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns; wherein the leukocyte filtered blood product has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtered blood product produced by a method comprising: supplying a blood product to be filtered of leukocytes to a prefilter, and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns; wherein said leukocyte filtered blood product has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtered blood product produced by a method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter having at least 5% of its pore volume constituted by pores having a pore cross section diameter larger than 10 microns; wherein said leukocyte filtered blood product has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtered blood product produced by a method comprising: supplying a blood product to be filtered of leukocytes to a prefilter; and supplying prefiltered blood product to a membrane filter downstream of the prefilter, said membrane filter being characterized in that no more than 30% of its pore volume is constituted by pores having a pore cross section diameter less than 3 microns; wherein said leukocyte filtered blood product has had the content of at least one blood component removed or reduced, relative to the content of said at least one component in whole blood, prior to the step of supplying the blood product to be filtered of leukocytes to the prefilter.
There is also provided, in accordance with a preferred embodiment of the invention, a leukocyte filtering method, comprising: supplying whole blood to a prefilter; and supplying prefiltered blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it comprises at least two non-cellulosic membranes having generally the same degree of symmetry and each having a thickness of less than about 0.25 mm; characterized in that the prefilter and membrane filter, operating together, reduce the number of leukocytes present in one unit of whole blood to no more than five million. In accordance with a preferred embodiment of the invention, the prefilter and membrane filter, operating together, reduce the number of leukocytes present in one unit of whole blood to no more than one million. In accordance with a preferred embodiment of the invention, the filtered blood product also contains at least 60% of the platelets contained in the whole blood before filtration and at least 85% of the red cells contained in the whole blood before filtration.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: whole blood to a prefilter which captures less than 60% of incoming leukocytes; and supplying prefiltered whole blood to a non-cellulosic and generally homogeneous membrane filter. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger that 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 50% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the non-cellulosic membrane is a generally homogeneous membrane. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, and membrane filter being characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter comprising at least one layer of a non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the non-cellulosic membrane is a generally homogeneous membrane. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter having at least 5% of its pore volume constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention a leukocyte filtering method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that no more than 30% of its pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood characterized in that: it includes (i) less than one million leukocytes per unit of blood, and (ii) at least one of: (a) at least sixty percent of the number of platelets in non-filtered whole blood; and (b) at least ninety percent of the number of red cells in non-filtered whole blood. In accordance with a preferred embodiment of the invention, the leukocyte filtered whole blood is characterized in that it includes: at least sixty percent of the number of platelets in non-filtered whole blood; and at least ninety percent of the number of red cells in non-filtered whole blood. In accordance with a preferred embodiment of the invention, the leukocyte filtered whole blood is produced by a method including: supplying whole blood to a prefilter which captures less than 60% of incoming leukocytes; and supplying prefiltered whole blood to a non-cellulosic and generally homogenous membrane filter. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membranes filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume being constituted by pores having a pore cross section diameter less than 3 microns. In accordance with a preferred embodiment of the invention, the leukocyte filtered whole blood is produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the leukocyte filtered whole blood is produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the leukocyte filtered whole blood is produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the leukocyte filtered whole blood is produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the leukocyte filtered whole blood is produced by a method comprising; supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter having at least 5% of its pore volume constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the leukocyte filtered blood product is produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter; said membrane filter being characterized in that no more than 30% of its pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood produced by a method including: supplying whole blood to a prefilter which captures less than 60% of incoming leukocytes; and supplying prefiltered whole blood to a non-cellulosic and generally homogeneous membrane filter. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane. In accordance with a preferred embodiment of the invention, the membrane filter comprises at least one layer of a generally homogeneous non-cellulosic membrane, wherein the total pore volume of pores having a diameter between 1-30 microns is less than 90% of the total pore volume. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that at least 5% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In accordance with a preferred embodiment of the invention, the membrane filter is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane volume ratio larger than 6 square meters per milliliter of membrane volume.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood produced by a method comprising: supplying whole blood to be filtered of leukocytes to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore surface area/membrane mass ratio larger than 12 square meters per gram of membrane.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood produced by a method comprising: supplying whole blood to be filtered of leukocytes to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that it has a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that at least 40% of its pore volume is constituted by pores having a pore cross section diameter of between 3 and 10 microns.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood product produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter having at least 5% of its pore volume constituted by pores having a pore cross section diameter larger than 10 microns.
There is also provided in accordance with a preferred embodiment of the invention leukocyte filtered whole blood produced by a method comprising: supplying whole blood to a prefilter; and supplying prefiltered whole blood to a membrane filter downstream of the prefilter, said membrane filter being characterized in that no more than 30% of its pore volume is constituted by pores having a pore cross section diameter less than 3 microns.
In the context of the present application, the following definitions are used throughout:
xe2x80x9cPore sizexe2x80x9d is pore diameter in microns or other units of length, calculated as a function of mercury intrusion pressure, assuming cylindrical pores and the appropriate value of mercury surface tension and contact angle.
xe2x80x9cMedian pore sizexe2x80x9d is that pore size, above and below which the same volume of mercury is pressed into the membrane, e.g. if the median pore size is 10 microns, then the total amount mercury in all pores of a size less than 10 microns is the same as the total amount of mercury in all pores of a size greater than 10 microns.
xe2x80x9cPore size distributionxe2x80x9d is the population frequency distribution of pores whose size is determined as described above.
xe2x80x9cCumulative pore volumexe2x80x9d is the total mercury volume pressed into pores of a given size range.
xe2x80x9cSymmetric membranexe2x80x9d and xe2x80x9chomogeneous membranexe2x80x9d are used synonymously to refer to a membrane wherein most pores of the membrane maintain approximately the same pore cross sectional diameter along the entire length of the pore through the thickness of the membrane structure, irrespective of the pore size distribution in the membrane.
xe2x80x9cPore cross section diameterxe2x80x9d (or xe2x80x9cpore diameterxe2x80x9d) is the diameter of the pore (assumed to be cylindrical) calculated as described above. xe2x80x9cPore sizexe2x80x9d and xe2x80x9cpore diameterxe2x80x9d are used synonymously throughout the present description and claims.
The present invention also seeks to provide a novel membrane leukoreduction filter, a filtering method and filtering blood products. The present inventors have found that contrary to teachings of the prior art, certain commercial membranes can be used to make efficient leukoreduction filters. Also, simpler structures than previously conceived were found to make for highly efficient filters. These novel structures comprise only two groups of layers, wherein individual layers within each group are generally identical (and need not have gradually or step-wise diminishing pore sizes or be arranged to have gradually or step-wise diminishing pore sizes). The first group acts as preliminary filter (prefilter), capturing gel particles, microaggregates and a certain fraction of the leukocytes. The second group of identical layers captures the remaining fraction of leukocytes.
The preliminary filter layer is typically made of non-woven sheets with relatively large diameter fibers (3.5-10 microns in diameter), although woven sheets and membranes not necessarily of the same structure as the filter membranes may also be employed for this purpose. The second layer is typically made of identical membrane sheets having a median pore size of 3-12 microns. In contrast to the teachings of the prior art, it was found that the membranes do not need to have an especially narrow pore size distribution (such as the total volume of pores of 2-30 micron size constituting more than 94% of the total pore volume). It was also found, in contrast to the teaching of the prior art that when used in accordance with the present invention, the non-woven sheets can be made of relatively large diameter fibers (3.5-10 microns vs. 1-3 microns as taught in the prior art). The filters of the present invention can be used without any post-treatment to filter packed red cell units or whole blood. If it is desired to recover platelets from either whole blood or platelet concentrates, the membrane and prefilter can be chemically treated to provide media combining efficient white cell retention and good platelet and red cell recovery (e.g. by the method described in U.S. Pat. No. 5,783,094, the disclosure of which is incorporated herein by reference).
In a preferred embodiment of the present invention, the filter is constructed of two groups of layers, each group containing generally identical layers of filter media. One group comprises non-cellulosic membranes, while the other group comprises the prefilter material, preferably non-woven sheets.
The group of membranes can be made of any biocompatible non-cellulosic polymer composition. For example nylon, polyvinyl chloride (PVC), PVC copoylmers, polyvinylidene fluoride sulfone polymers, polyester, polyketones, aromatic polyamides, polyimides, polycarbonate, polyphenylene oxide, polyvinyl acetate and the like can be used to form the membranes of the present invention. The membranes can be manufactured by processes known in the art, including but not limited to solution phase separation, thermal inversion, foaming and sintering. Preferably, the thickness of each membrane is less than 0.25 mm, preferably of thickness between about 0.05 mm and about 0.2 mm. As analyzed by mercury porosimetry, the membrane filter preferably has a median pore size of 3.0-12 xcexcm.
In contrast to the teachings of the prior art, pore size distribution does not need to be especially narrow. Typically, pores in the range of 2-30 xcexcm preferably constitute less than 94% of the total pore volume of the membrane. Also, in contrast to the teachings of the prior art, in a preferred embodiment of the invention, the membrane is essentially symmetrical and isotropic, having homogeneous pores throughout its bulk.
When a group of non-woven sheets is used in a prefilter or as a prefilter for the membrane, the group of sheets preferably has a mean fiber diameter larger than that necessary in filters of the prior art in which leukocytes are captured mostly by the non-woven material. The most preferred mean fiber diameter is 3.5-10 xcexcm. The non-woven sheets can be made of various biocompatible materials, e.g., polyester, nylon, polypropylene, cellulose derivatives and the like. It will be understood, however, that other materials can be used in the construction of the prefilter portion, such as woven sheets or membranes having a pore structure and/or pore size distribution not necessarily the same as the pore structure or pore size distribution of the membranes used to construct the filter portion of the leukocyte filter.
Prior art methods for filtering blood, particularly whole blood, employ a prefilter, generally to prevent clogging of the filter membranes. The prefilters of the prior art may themselves be layers of membranes, or they may be woven or non-woven sheets. However, contrary to the teachings of the prior art, in accordance with the present invention the thickness of the prefilter, whether a group of non-woven sheets or other material, will typically be more than 0.5 mm. Also, in contrast to the prior art, in the present invention the group of preliminary filter layers (whether fabricated from non-woven sheets or from other materials, such as membranes different from the membranes or group of membranes used in the filter portion) can be made to capture less than 60% of all leukocytes, and the leukocyte filter will still be highly efficient in both leukocyte retention and volume recovery.
In constructing a leukocyte filter according to one preferred embodiment of the present invention, at least two membrane layers are stacked with at least two non-woven sheets and placed in an appropriate housing made of biocompatible plastic. Whole blood or blood fractions are allowed to flow through the filter by gravity. According to another preferred embodiment of the present invention a single membrane layer is stacked with at least two layers of non-woven sheets to make a leukocyte filter.
The membrane and non-woven fabric layers can be either untreated or treated. When untreated, whole blood and packed red cells can be efficiently leukoreduced. Platelets in whole blood are also retained by a filter so constructed. If it is desired to recover platelets from either whole blood or platelet-containing blood fractions, the filter media (both membrane and non-woven) need to be chemically treated to prevent blockage of the platelets. Such treatments can be, although need not necessarily be, in accordance with that described in U.S. Pat. No. 5,783,094, assigned to the present applicant/assignee, the disclosure of which is incorporated herein by reference. Such treatment efficiently coats all external and internal surfaces of the filter media and renders them platelet compatible. Physical and mechanical properties of the media are not affected by the treatment.